AJP - Gastrointestinal and Liver Physiology, Vol 251, Issue 5 575-G584, Copyright © 1986 by American Physiological Society
Associations between transports of alanine and cations across cell membrane in rat hepatocytes
L. O. Kristensen
Alanine transport across the liver cell membrane is a regulated key process
in the amino acid metabolism of the body. The majority of alanine influx in
hepatocytes is Na+ dependent and is stimulated by intracellular negativity.
The molar ratio between cotransported Na+ and alanine is 1:1. Alanine
efflux is stimulated by intracellular Na+, whereas the role of the membrane
potential is unclear. The transmembrane Na+ electrochemical gradient seems
to be the exclusive driving force for cellular alanine accumulation. At a
physiological Na+ gradient, intracellular alanine can exceed the
extracellular concentration about 20-fold, but metabolism will exert a
conspicuous sink effect. Na+-coupled uptake of alanine appears to be a
challenge that triggers a sequence of regulatory events: increased cellular
Na+ leads to an increase in active Na+-K+-pumping and thus in K+ influx;
influx of alanine and cations tends to increase the cellular content of
osmotically active substances implying a tendency to water uptake; cell
swelling, even when modest, induces an increase in the permeability of a
conductive pathway for K+ leading to net efflux of K+ (with accompanying
anions) and cellular hyperpolarization. Net efflux of K+ prevents excessive
cell volume increase during amino acid accumulation, whereas
hyperpolarization tends to support the driving force for alanine influx
(and anion efflux). The pathway for K+ efflux needs further
characterization, but it may involve single-file diffusion with Ca2+ as an
activator. This model suggests that cell volume regulatory processes mainly
serve to compensate for changes in intracellular content of ions and
metabolites during activation of specialized cellular processes.
